Altogether, we establish the first in vivo human AML model, which provides evidence that AML may originate in a PPARG‐activated renal MSC lineage that is skewed toward adipocytes and smooth muscle and away from osteoblasts, and uncover PPARG as a regulator of AML growth, which could serve as an attractive therapeutic target. The gene discussed is PPARG; the disease is acute myeloid leukemia.